Endogenous Adrenocorticotropic Hormone Research Articles

A quantitative modeling framework to understand the physiology of the hypothalamic-pituitary-adrenal axis and interaction with cortisol replacement therapy.

Congenital adrenal hyperplasia (CAH) is characterized by impaired adrenal cortisol production. Hydrocortisone (synthetic cortisol) is the drug-of-choice for cortisol replacement therapy, aiming to mimic physiological cortisol circadian rhythm. The hypothalamic-pituitary-adrenal (HPA) axis controls cortisol production through the pituitary adrenocorticotropic hormone (ACTH) and feedback mechanisms. The aim of this study was to quantify key mechanisms involved in the HPA axis activity regulation and their interaction with hydrocortisone therapy. Data from 30 healthy volunteers was leveraged: Endogenous ACTH and cortisol concentrations without any intervention as well as cortisol concentrations measured after dexamethasone suppression and single dose administration of (i) 0.5-10mg hydrocortisone as granules, (ii) 20mg hydrocortisone as granules and intravenous bolus. A stepwise model development workflow was used: A newly developed model for endogenous ACTH and cortisol was merged with a refined hydrocortisone pharmacokinetic model. The joint model was used to simulate ACTH and cortisol trajectories in CAH patients with varying degrees of enzyme deficiency, with or without hydrocortisone administration, and healthy individuals. Time-dependent ACTH-driven endogenous cortisol production and cortisol-mediated feedback inhibition of ACTH secretion processes were quantified and implemented in the model. Comparison of simulated ACTH and cortisol trajectories between CAH patients and healthy individuals showed the importance of administering hydrocortisone before morning ACTH secretion peak time to suppress ACTH overproduction observed in untreated CAH patients. The developed framework allowed to gain insights on the physiological mechanisms of the HPA axis regulation, its perturbations in CAH and interaction with hydrocortisone administration, paving the way towards cortisol replacement therapy optimization.

The impact of single-dose trazodone administration on plasma endogenous adrenocorticotropic hormone and serum cortisol concentrations in healthy dogs.

Conditions affecting the hypothalamic-pituitary-adrenal (HPA) axis are common in dogs. Testing the function of the HPA axis includes measurement of endogenous adrenocorticotropic hormone (eACTH) and performance of an adrenocorticotropic hormone (ACTH) stimulation test. Trazodone is commonly administered to dogs to decrease stress. In humans, trazodone significantly decreases plasma cortisol concentration via alpha-1 adrenergic activity. Determine the influence of trazodone on eACTH and serum cortisol concentrations in healthy dogs. Fourteen healthy, adult, companion dogs. Prospective, randomized placebo-controlled study. Trazodone (8-10 mg/kg) or placebo was administered PO 1 hour before eACTH measurement and ACTH stimulation testing. After a ≥7-day wash-out period, dogs received the opposite treatment. Differences in eACTH, pre- and post-ACTH stimulation cortisol concentrations, and delta (difference between pre- and post-ACTH) cortisol concentrations were analyzed using a paired t or signed-rank test with a P < .05 significance level. The eACTH concentrations were not significantly different (P = .23) between treatments. Similarly, no significant differences were found in the pre-ACTH cortisol concentrations between treatments (P = .40). Post-ACTH cortisol concentrations (P = .05) and delta cortisol concentrations (P = .04) were significantly lower when the dogs were treated with trazodone. Preliminary data suggest trazodone administration dampens the adrenocortical response to stimulation in healthy dogs. If similar effects are found in dogs with adrenal disease, the use of trazodone may affect diagnosis and clinical decision making in these populations.

Stress response as a contributing factor in horses with laminitis.

Laminitis is a complex and debilitating disease of horses. Numerous predisposing factors contribute to laminitis development, however the exact pathogenesis remains undetermined. Serum T4, cortisol, and histamine are components of the innate stress response and could play a causative or contributory role. Stress hormone concentrations in laminitis are largely unknown. To evaluate parameters associated with stress response in horses with laminitis, and compare these to healthy horses and horses with gastrointestinal (GI) disease. Thirty-eight adult horses presenting for non-medical conditions, GI abnormalities, or clinical laminitis were prospectively enrolled. Horses were assigned to the appropriate disease group (healthy, GI disease, and laminitis) and had blood drawn on presentation to the hospital. Samples were analyzed for plasma endogenous adrenocorticotrophic hormone (eACTH), serum cortisol, serum thyroid hormone, and plasma histamine. Stress hormone concentrations were significantly different between horses in the laminitis and GI disease groups. Plasma histamine levels were highest in horses with laminitis, compared with GI disease and controls. Both horses with laminitis and GI disease had increased plasma eACTH when compared to healthy horses. Horses with GI disease had higher serum cortisol concentrations than horses with laminitis or controls. Serum T4 was lower in horses with GI disease than in horses with laminitis and controls. Horses with laminitis had relative increases in both plasma histamine and eACTH concentrations. Serum T4 and cortisol concentrations of horses with laminitis did not differ significantly when compared to healthy horses. The role of stress hormones in equine disease warrants further investigation.

Adrenocorticotropic hormone-producing pituitary adenoma with pituitary apoplexy treated by surgical decompression: a case report

BackgroundPituitary-dependent hypercortisolism (PDH) is one of the most common endocrine disorders in veterinary medicine. However, there are few reports on pituitary tumor apoplexy (PTA) in dogs and no reports on its surgical intervention in veterinary medicine. Accordingly, the appropriate treatment is unknown. Herein, a case of PDH and PTA in a dog treated surgically is described.Case presentationA mongrel female dog (spayed; age, 8 years and 8 months; weight, 6.1 kg) with persistently elevated alkaline phosphatase underwent adrenocorticotropic hormone (ACTH) stimulation testing (post-stimulation cortisol: 20.5 μg/dL), abdominal ultrasonography (adrenal gland thickness: left, 5.7 mm; right, 8.1 mm), and brain magnetic resonance imaging (MRI) (pituitary-to-brain ratio [PBR], 0.61) at the referral hospital, resulting in a diagnosis of PDH (day 0). On day 9, the dog visited XXXX for the preparation of pituitary surgery to treat PDH. However, on days 10–15, the dog developed a loss of energy and appetite, bloody diarrhea, vomiting, and a decreased level of consciousness. However, on day 16, the dog’s condition recovered. A preoperative MRI scan performed on day 52 (the day of surgery) showed apoplexy in the dorsal pituitary region (PBR, 0.68). Based on the PTA findings, the risks of surgery were described to the owner, and approval was obtained. At the time of trans-sphenoidal surgery, a partial pituitary resection was performed with preservation of the PTA area due to adhesions between the PTA area of the right side of the pituitary and surrounding tissues. The resected pituitary tissue was diagnosed as an ACTH-producing adenoma, with necrotic and hemorrhagic findings. As of day 290, endogenous ACTH and cortisol levels did not exceed the reference range.ConclusionsThe acute signs that occurred on days 10–15 were most likely caused by PTA. Therefore, when signs similar to those detected in acute hypoadrenocorticism are observed in dogs with PDH, it is necessary to include PTA as a differential diagnosis. Trans-sphenoidal surgery may be effective in PDH-affected dogs that develop PTA, but careful attention should be paid to tissue adhesions secondary to hemorrhage that may occur after PTA.

Temporally specific adrenocorticotropic hormone reference intervals for horses in South Africa

An endogenous adrenocorticotropic hormone (ACTH) concentration above the reference interval (RI) is commonly used as means for diagnosing equine pituitary pars intermedia dysfunction (PPID). Basal ACTH concentrations are highly dependent on photoperiod and RIs should be month- and location-specific. To date, no ACTH RIs have been specifically established for South Africa. This study aimed to determine geographically and seasonally relevant RIs for equine ACTH in the Gauteng province of South Africa. A longitudinal prospective study was conducted over twelve months to determine ACTH RIs for a representative population of healthy South African horses in the Gauteng province. Eighty clinically healthy horses under 12 years of age were recruited for monthly venous blood sample collection, from July 2019 to June 2020. ACTH was measured using a chemiluminescent assay. RIs were constructed for each month of the year. This South African population showed similar temporal changes in ACTH concentrations to those previously observed in other locations. Upper reference limits were at their lowest in early summer (21.4 pg/ml, 90% CI 20.8-21.7) with a pronounced increase in autumn (60.6 pg/ml, 90% CI 53.1-62.7), and tapered off in winter (22.3 pg/ml, 90% CI 19.9-23.2). The month-specific ACTH RIs generated in this study will improve the accuracy of diagnosis and monitoring of PPID in the local equine population. These results highlighted the previously recommended need for seasonal and location-specific RIs.

Seasonal variation of endogenous adrenocorticotropic hormone concentrations in healthy non-geriatric donkeys in Northern California

Elevated plasma adrenocorticotropic hormone (ACTH) is often used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. The hormone naturally increases in the fall in horses, and donkeys have been found to have higher ACTH concentrations than horses. However, circannual variation of ACTH has not been assessed in donkeys. The objective of the study was to establish seasonal variation of basal plasma ACTH concentrations over the course of a year in clinically healthy, non-geriatric donkeys. It was hypothesized that donkey ACTH concentrations would be higher than those reported in horses without PPID in all seasons, and that, similarly to horses, ACTH concentrations would further increase in the fall months. Twenty-six healthy adult donkeys (10 standards, 16 miniatures), a median (range) of 6 (2–13) years of age, were included. Donkeys were housed at a single location. Serial plasma samples were obtained monthly for 12 months. Plasma ACTH concentrations were determined by immunoassay. Data are presented as median (range), with a P-value < 0.05 considered significant. ACTH concentrations were lowest in the winter and spring [12.8 (5.0–73.6) pg/ml and 12.5 (2.8–62.6) pg/ml, respectively], with an increase in the summer [53.2 (29.7–305.0) pg/ml], and peak in the fall [77.1 (12.4–319.0) pg/ml]. ACTH concentrations were highest in the month of September [122.0 (41.7–319.0) pg/ml]. Donkey ACTH concentrations were higher than equine reference ranges from May through November but showed similar circannual variation with dramatic increases in the fall months. Species-specific reference ranges are necessary for accurate interpretation of endocrinopathy screenings in donkeys.

Трудности и ошибки диагностики вторичного гипокортицизма у больных старческого возраста

Adrenal insufficiency is a relatively rare condition, especially among individuals older than 65 years. Therefore, the specific manifestations of primary and secondary adrenal insufficiency are understudied in elderly patients. The article elucidates new data on the senile physiological hyperplasia of the zona fasiculata of the adrenal cortex: human aging is tightly linked to an increasing secretion of glucocorticoids. A clinical case of secondary adrenal insufficiency due to empty sella syndrome (ESS) and hydrocephalus in a senile patient is described. The patient’s medical history included two key elements aggravating the adrenal insufficiency: adrenalectomy and chemotherapy with platinum derivatives which could have impact on the adrenal glands. The specific symptoms experienced by the patient and the clinical course of the disease correlated with the residual secretion of adrenocorticotropic hormone (ACTH), cerebral disorders (ESS) and the compensatory secretion of corticotropin releasing factor. The clinical presentation of adrenal insufficiency was vague and atypical. In addition, it was found that the patient had hyposecretion of anabolic androgenic steroids. In turn, it caused a muscle hypotrophy and facilitated the recurrence of pelvic organ prolapse after the earlier performed pelvic floor reconstructive surgery. In such clinical cases the treatment should be aimed at improving the state of the hypothalamic-pituitary system and increasing the production of endogenous corticotropin releasing factor, ACTH, and cortisol. Androgen replacement therapy in androgen-deficient elderly patients has not been developed. KEYWORDS: secondary adrenal insufficiency, adrenocorticotropic hormone; empty sella syndrome, glucocorticoids. FOR CITATION: Tereshchenko I.V. Difficulties and diagnostic errors in old patients with secondary adrenal insufficiency. Russian Medical Inquiry. 2022;6(9):534–537 (in Russ.). DOI: 10.32364/2587-6821-2022-6-9-534-537.

Successful treatment of feline hyperadrenocorticism with pituitary macroadenoma using radiation therapy: a case study.

A 10-year-old castrated male cat showing behavioral (irritation, prowling, and tumbling) and cutaneous abnormalities such as dermal fragility was diagnosed as hyperadrenocorticism with pituitary macroadenoma, concurrent with insulin dependent diabetes mellitus. Pituitary enlargement (18.0 mm) was observed during magnetic resonance imaging. High endogenous adrenocorticotropic hormone levels (>2,500 pg/ml) were also observed. Although trilostane treatment (5–10 mg/head, daily) was commenced, the clinical signs did not disappear. Insulin and trilostane treatment were discontinued on day 86 after first day of radiation therapy (4 Gy/12 fractions). After radiation therapy, a decreased pituitary tumor size (10.7 mm) was observed on day 301; neurological and dermatological signs exhibited remission. Radiation therapy is the treatment of choice for feline hyperadrenocorticism with pituitary macroadenoma with neurological signs.

Utility of a corticotropin-releasing hormone test to differentiate pituitary-dependent hyperadrenocorticism from cortisol-producing adrenal tumors in dogs.

BackgroundHyperadrenocorticism (HAC) is a common endocrine disorder in dogs; however, there are no reports on the use of the corticotropin‐releasing hormone test (CRHT) to differentiate between pituitary‐dependent hyperadrenocorticism (PDH) and cortisol‐producing adrenal tumors (CPATs), both causative of HAC.ObjectivesTo evaluate the usefulness of CRHT as a tool to differentiate between PDH and CPAT in dogs and to determine the reference intervals for CRHT in healthy, PDH, and CPAT dogs.AnimalsDogs diagnosed with PDH (n = 21), CPAT (n = 6), and healthy beagle dogs (n = 33).MethodsThis prospective study included dogs with a definitive diagnosis of PDH and CPAT and healthy beagle dogs, in which CRHT was performed, were prospectively evaluated. We investigated the correlations of CRHT (endogenous adrenocorticotropic hormone [ACTH] concentration, endogenous ACTH concentration [EAC], and poststimulation ACTH concentration [PAC]) with pituitary‐to‐brain ratio (PBR) (in PDH) and with indices of adrenal ultrasonography (smaller and larger adrenal gland dorsoventral thickness in PDH and CPAT).ResultsFor EAC, the area under the curve (AUC) was 0.95, with a cutoff value of 26.3 pg/mL (sensitivity: 90.62%, specificity: 87.50%). The AUC for PAC was 0.96 with a cutoff value of 54.5 pg/mL (sensitivity: 100.00%, specificity: 66.67%). The 95% reference interval for CRHT in healthy (control) dogs ranged 5.00 to 79.8 pg/mL (1.10‐17.57 pmol/L) for EAC, and 1.92 to 153.42 pg/mL (0.42‐33.78 pmol/L) for PAC. There was no significant correlation between PBR and CRHT, nor adrenal size and CRHT.Conclusions and Clinical ImportanceCRHT appears to be a rapid and reliable test for differentiating PDH from CPAT in dogs.

Localized alopecia and suppression of hypothalamic-pituitary-adrenal (HPA) axis in dogs following treatment with difluprednate 0.05% ophthalmic emulsion (Durezol\xae)

BackgroundDespite the common use of topical ophthalmic corticosteroids in dogs, detailed reports on systemic and dermatologic adverse effects are limited.ResultsNine purpose-bred research Beagles were treated with difluprednate 0.05% ophthalmic emulsion in one or both eyes 2–3 times daily. Some difluprednate treated dogs developed mild to severe alopecia of the periocular region, face, and distal pinna (5/9). The median duration of treatment prior to onset of dermatologic signs for difluprednate treated dogs was 550 days (453–1160 days). Diagnostic testing included complete blood count (CBC) and serum biochemistry, adrenocorticotropic hormone (ACTH) stimulation testing combined with endogenous ACTH measurement, and skin biopsy. The CBC and chemistry were within normal limits for all dogs. There were varying degrees of suppression of the hypothalamic-pituitary-adrenocortical (HPA) axis with difluprednate treatment. Dogs with the most profound alopecic changes had less pronounced HPA axis suppression compared to dogs with no integumentary changes. Skin biopsies demonstrated follicular atrophy and follicular keratosis. When topical difluprednate was reduced to unilateral therapy, the hair regrew on the untreated side of the face. In addition to the affected research dogs, a 7-year old female spayed Chihuahua that was being treated as a clinical patient with long-term difluprednate 0.05% ophthalmic emulsion developed generalized hypotrichosis on the head and body and a potbellied appearance. ACTH stimulation testing revealed suppression of the HPA axis with a mild increase in serum alkaline phosphatase (ALP) activity and a urine specific gravity of 1.016. The combination of clinical signs and laboratory abnormalities was supportive of iatrogenic hyperadrenocorticism.ConclusionsIn dogs long-term use of difluprednate ophthalmic emulsion results in HPA axis suppression and in some cases iatrogenic hyperadrenocorticism. A novel pattern of localized alopecia is suspected to be related to dermal absorption and local action due to superior potency and penetration compared to other commonly utilized ophthalmic corticosteroids.

Vitamin A failed to ameliorate clinical signs in dogs with pituitary-dependent hypercortisolaemia.

In dogs with pituitary-dependent hypercortisolaemia, retinoic acid was shown to lower cortisol, reduce pituitary tumour size and decrease clinical signs when administered for six months. Oral vitamin A (retinol) has been used to treat various canine dermatoses in which retinoic acid has been efficacious. To determine if orally administered vitamin A lowers cortisol and reduces clinical signs in dogs with pituitary-dependent hypercortisolaemia over a five month period. Five dogs were enrolled in this study. Diagnosis of hypercortisolaemia was based on the presence of at least three clinical signs and one abnormal screening test. Diagnosis of pituitary-dependent disease was based on low dose dexamethasone suppression (LDDS) test results and symmetrical adrenal glands on ultrasound. Adrenocorticotropic hormone (ACTH) stimulation testing and adrenal ultrasound were performed at each visit. Plasma was collected at each visit and stored at -80°C for batch analysis of endogenous ACTH at conclusion of the study. Four dogs completed the study. A fifth dog died from complications of hypercortisolaemia before the third month. One dog showed improvement in clinical signs, yet there was no significant decrease in adrenal gland size or cortisol concentrations. Endogenous ACTH concentrations at the fifth month were decreased from baseline in two dogs and increased from baseline in one dog. The treatment had no adverse effects. Results from this study failed to show an improvement in clinical signs or cortisol concentration after five months of oral daily vitamin A in dogs with hypercortisolaemia.

Canine endogenous adrenocorticotrophic hormone preanalytical stability after sample shipping in dry ice or recyclable ice bars

ABSTRACT: Endogenous adrenocorticotrophic hormone (eACTH) measurement is useful in hypercortisolism and hypoadrenocorticism investigation; however, since the hormone is highly unstable, blood samples require proper processing and storage, as well as shipping is often a step limiting since few laboratories offer this assay in Brazil. The aim of this note was to compare overnight dog´s eACTH preanalytical stability when frozen samples were shipped in dry ice (DI), or with recyclable ice bars (RIB). A total of 56 paired samples for eACTH measurement were analyzed. Blood samples were properly handled, plasma aliquots transferred into plastic microtubes, and stored at -80ºC. The fifty-six paired samples were overnight shipped in two thermic isolated boxes with DI or involved by RIB. Despite there was a high correlation between results from both shipping methods (r Spearman = 0.958, P&lt;0.001), the Wilcoxon matched-pairs rank test showed that the shipping method may influence results (P&lt;0.001). However, this difference does not affect results interpretation. By this way, when DI shipping was not possible, RIB shipping may represent a risk to eACTH preanalytical stability.

Adrenal function evaluation in critically ill dogs with low doses of synthetic ACTH

The hypothalamus-pituitary-adrenal axis function may be impaired in patients with critical illnesses, especially cases of sepsis, named critical illness-related corticosteroid insufficiency (CIRCI). This study examined the function of the hypothalamic-pituitary-adrenal axis in normal dogs (n = 10) and dogs with critical diseases (n = 16), through determinations of endogenous ACTH (adrenocorticotropic hormone), basal cortisol and cortisol after stimulation in low doses of synthetic ACTH (1.0μg/kg/IV). The stimulation test with ACTH dose tested was verified as effective for evaluation of adrenal function in healthy and sick dogs. Ill dogs differed from healthy dogs by presenting higher basal cortisol values. Eight sick dogs presented a decrease in endogenous ACTH, basal cortisol, or Δ-cortisol. No significant differences were found between the control groups and critically ill dogs for the values of endogenous ACTH, cortisol after stimulation or Δ-cortisol. We concluded that the stimulation test with low-dose ACTH was effective for evaluation of adrenal function, as well as the fact that a considerable portion of critically ill dogs studied here, especially with sepsis, had evidence of inadequate corticosteroid response to stress.

Clinical features and their course of pituitary carcinoma with distant metastasis in a dog

An 11-year-old male toy poodle with neurological symptoms was diagnosed with a macroscopic pituitary tumor, which produced adrenocorticotropic hormone. Radiation therapy with a linear accelerator was performed for the pituitary tumor, and resulted in good local tumor control. However, serum endogenous adrenocorticotropic hormone concentrations were uncontrollable even after the tumor disappeared. Abdominal computed tomography revealed splenic masses, and splenectomy was performed. Histopathological examination of the surgical specimen showed tumor cells with eosinophilic and finely granular cytoplasm suggestive of endocrine origin. Since these cells were positive for adrenocorticotropic hormone, the case was diagnosed as a pituitary carcinoma with distant metastasis. Necropsy revealed multiple metastases to the abdominal organs. This is the first case report describing canine pituitary carcinoma with distant metastasis.

Multiple adrenocortical steroid response to administration of exogenous adrenocorticotropic hormone to hospitalized foals.

BackgroundThe hypothalamic‐pituitary‐adrenal axis regulates the response to sepsis‐associated stress. Relative adrenal insufficiency or adrenocorticotropic hormone (ACTH):cortisol imbalance, defined as a poor cortisol response to administration of ACTH, is common and associated with death in hospitalized foals. However, information on other adrenal steroid response to ACTH stimulation in sick foals is minimal.ObjectiveTo investigate the response of multiple adrenocortical steroids to administration of ACTH in foals.AnimalsHospitalized (n = 34) and healthy (n = 13) foals.MethodsIn this prospective study, hospitalized foals were categorized into 2 groups using cluster analysis based on adrenal steroids response to ACTH stimulation: Cluster 1 (n = 11) and Cluster 2 (n = 23). After baseline blood sample collection, foals received 10 μg of ACTH with additional samples collected at 30 and 90 minutes after ACTH. Steroid and ACTH concentrations were determined by immunoassays. The area under the curve (AUC) and Delta0‐30 were calculated for each hormone.ResultsThe AUC for cortisol, aldosterone, androstenedione, pregnenolone, 17α‐OH‐progesterone, and progesterone were higher in critically ill (Cluster 1) compared to healthy foals (P < .01). Delta0‐30 for cortisol and 17α‐OH‐progesterone was lower in Cluster 1 (24%, 26.7%) and Cluster 2 (16%, 11.2%) compared to healthy foals (125%, 71%), respectively (P < .05). Foals that died had increased AUC for endogenous ACTH (269 versus 76.4 pg/mL/h, P < .05) accompanied by a low AUC for cortisol (5.5 versus 15.5 μg/dL/h, P < .05), suggesting adrenocortical dysfunction.Conclusion and Clinical ImportanceThe 17α‐OH‐progesterone response to administration of ACTH was a good predictor of disease severity and death in hospitalized foals.

Hypoadrenocorticism in two cats successfully treated with desoxycorticosterone pivalate

Two cats were presented with lethargy and anorexia. Clinically, the cats showed hypothermia and dehydration. Blood examination in both cats showed hyponatraemia, hyperkalaemia and additionally azotaemia in case 1 and...

Effective Medical Therapy for Cushing Disease Can Increase the Susceptibility to Relative Hypocortisolism

ABSTRACT Objective: Pasireotide is approved for treatment of adults with Cushing disease (CD) with persistent hypercortisolism for whom surgery has failed or is not an option. Effective medical therapy for CD may increase the susceptibility of relative hypocortisolism during acute stress because of a patient's inability to compensate by increasing endogenous adrenocorticotropic hormone (ACTH) and cortisol secretion. We describe a patient with CD on pasireotide therapy for 7 years in whom biochemical eucortisolemia was achieved but subsequently experienced several distinct episodes of relative hypocortisolism during periods of acute illness. Methods: A 67-year-old man with biochemical confirmation of CD exhibited clinical and biochemical features of persistent hypercortisolism after transsphenoidal surgery despite pituitary magnetic resonance imaging showing no residual or recurrent tumor. He was enrolled into a phase 3 study (NCT00434148) and was initated on twice-daily subcutaneous pasireotide. Results: ...

The effect of orally administered Budesonide on the hypothalamic-pituitary-adrenal axis in dogs with inflammatory bowel disease

The aim of this study was to evaluate the effect of Budesonide on the hypothalamic-pituitary-adrenal (HPA) axis in dogs with inflammatory bowel disease. The effect of orally administered Budesonide (Entocort) on the HPA axis was analysed in 21 dogs with inflammatory bowel disease. Biochemical analyses were carried out to evaluate the activity levels of alanine aminotransferase, asparagine aminotransferase, alkaline phosphatase, cortisol and endogenous adrenocorticotropic hormone. Urine samples were collected from each patient before the study and after 30 days of the experiment to determine the composition and the physical and chemical properties of urine sediments. Considerably lower serum concentrations of cortisol and endogenous adrenocorticotropic hormone were observed after 30 days of treatment. A significant increase in alkaline phosphatase levels was noted on Day 30. In the studied dogs, the drop in HPA axis activity was correlated with side effects associated with the administered glucocorticosteroid (polyuria, polydipsia). In conclusion, we have shown that oral administration of Budesonide to dogs diagnosed with inflammatory bowel disease significantly suppressed the activity of the HPA axis.

A retrospective study of dogs with atypical hypoadrenocorticism: adiagnostic cut-off or continuum?

To describe the clinicopathologic findings and outcome in dogs with atypical hypoadrenocorticism (Group 1) and dogs with suspected atypical hypoadrenocorticism whose post-adrenocorticotropic hormone stimulation cortisol concentrations were greater than 55 nmol/L but below the laboratory reference interval (Group 2). Medical records were searched to identify dogs diagnosed with hypoadrenocorticism between January 2004 and June 2014. Dogs were excluded if their Na:K ratio was less than 27 or if they had received prior therapy that could interfere with adrenocorticotropic hormone stimulation testing. Forty dogs were included in Group 1 and nine dogs in Group 2. In Group 1, the most common biochemical abnormalities were hypoalbuminaemia (87%) and hypocholesterolaemia (76%). Of 35 dogs in Group 1 with follow-up biochemistry results, five (14%) developed electrolyte abnormalities at 2 to 51 months post diagnosis. Of seven dogs in Group 2 with follow-up, glucocorticoid therapy was discontinued in two dogs without return of clinical signs, four dogs were subsequently diagnosed with inflammatory bowel disease and one dog continued to have clinical signs despite glucocorticoid treatment. Dogs with gastrointestinal signs and hypoalbuminaemia and, or, hypocholesterolaemia should be evaluated for atypical hypoadrenocorticism. Follow-up electrolyte monitoring is recommended because some will develop electrolyte abnormalities. Although dogs in Group 2 had a clinical presentation compatible with atypical hypoadrenocorticism, the diagnosis appears unlikely based on review of follow-up data. Dogs with equivocal adrenocorticotropic hormone stimulation results should be evaluated for other underlying diseases such as inflammatory bowel disease. The use of endogenous adrenocorticotropic hormone measurements in these dogs warrants investigation.

Comparative effects of methylprednisolone and tetracosactide (ACTH 1–24 ) on ischemia/reperfusion injury of the rabbit spinal cord

IntroductionTetracosactide is an engineered peptide that applies the same biological impacts as the endogenous adrenocorticotropic hormone. Previous studies indicated that tetracosactide has anti-inflammatory, antioxidant and neurotrophic activity. In this study, we hypothesized that tetracosactide may have protective effects in spinal cord ischemia-reperfusion injury.Material and methodsRabbits were randomized into the accompanying four groups of eight animals each: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (tetracosactide). In the control group, just a laparotomy was performed. In the various groups, the spinal cord ischemia model was made by the impediment of the aorta only caudal to the renal vein. Neurological assessment was conducted with the Tarlov scoring system. Levels of myeloperoxidase, malondialdehyde and catalase were analyzed, similar to the activities of xanthine oxidase and caspase-3. Histopathological and ultrastructural assessments were additionally performed.ResultsAfter ischemia-reperfusion injury, increments were found in the tissue myeloperoxidase levels (p < 0.001), malondialdehyde levels (p < 0.001), xanthine oxidase action (p < 0.001) and caspase-3 movement (p < 0.001). Conversely, both serum and tissue catalase levels were diminished (p < 0.001 for both). After the administration of tetracosactide, declines were seen in the tissue myeloperoxidase levels (p < 0.001), malondialdehyde levels (p = 0.003), xanthine oxidase action (p < 0.001) and caspase-3 movement (p < 0.001). Conversely, both the serum and tissue catalase levels were expanded (p < 0.001). Besides, tetracosactide treatment indicated enhanced results related to the histopathological scores (p < 0.001), the ultra-structural score (p = 0.008) and the Tarlov scores (p < 0.001).ConclusionsThe findings showed for the first time that tetracosactide shows significant neuroprotective activity against ischemia-reperfusion injury of the spinal cord.